A New Single Gene Differential Biomarker for Mycobacterium tuberculosis Complex and Non-tuberculosis Mycobacteria

Abstract

Background Tuberculosis (TB) and non-tuberculous mycobacteriosis are serious threats to health worldwide. A simple non-sequencing method is needed for rapid diagnosis, especially in less experienced hospitals, but there is no specific biomarker commonly used for all mycobacteria. The ku gene of the prokaryotic error-prone non-homologous end joining system (NHEJ) has the potential to be a highly specific detection biomarker for mycobacteria. Methods A total of 7294 mycobacterial genomes and 14 complete genomes of other families belonging to Corynebacteriales with Mycobacteriaceae were downloaded and analyzed for the existence and variation of the ku gene. Mycobacterium tuberculosis complex (MTBC) and non-tuberculosis mycobacteria (NTM)- specific primers were designed and the actual amplification and identification efficiencies were tested with 150 strains of 40 Mycobacterium species and 10 kinds of common respiratory pathogenic bacteria. Results The ku gene of the NHEJ system was ubiquitous in all genome sequenced Mycobacterium species and absent in other families of Corynebacteriales . On the one hand, as a single gene non-sequencing biomarker, its specific primers could effectively distinguish mycobacteria from other bacteria, MTBC from NTM, which would make the clinical detection of mycobacteria easy and have great clinical practical value. On the other hand, the sequence of ku gene can effectively distinguish NTM to species level with high resolution. Conclusion The Ku protein existed before the differentiation of Mycobacterium species, which was an important protein involved in maintaining of the genome’s integrity and related to the special growth stage of mycobacteria. It was rare in prokaryotes. These features made it a highly special differential biomarker for Mycobacterium .

Non-Tuberculous Mycobacteria: Molecular and Physiological Bases of Virulence and Adaptation to Ecological Niches

“…In addition to the ability for extensive species characterization and categorization that is particularly relevant for the Mycobacterium genus, WGS enables the discovery of novel biomarkers helpful in the context of pathogen identification [ 17 ]. Recently, it was proposed the use of the ku gene as a biomarker for Mycobacterium genus [ 360 ]. In that study, 79.7% of all known mycobacterial species and all submitted genomes were considered for comparative genomics, indicating that this gene is widely distributed and conserved across Mycobacterium species [ 360 ].…”

“…Recently, it was proposed the use of the ku gene as a biomarker for Mycobacterium genus [ 360 ]. In that study, 79.7% of all known mycobacterial species and all submitted genomes were considered for comparative genomics, indicating that this gene is widely distributed and conserved across Mycobacterium species [ 360 ]. Gupta and coworkers (2018) indicate that ten conserved signature indels and nine conserved signature proteins are shared by most members of the Mycobacterium genus [ 13 ].…”

Biophysical and Computational Landscapes of Mycobacterial Pyrophosphatase: A Closer View of Drug Repurposing With Different Natural and Synthetic Compounds.

“…Therefore, deriving the proper medication against this malady is a primary need. This article is an attempt in the direction to deliver a more understanding view of Mycobacterium tuberculosis virulence and survival strategy [44][45]. Soluble inorganic pyrophosphatases (ppa) are essential proteins in Mycobacterium tuberculosis survival and depend on metal cofactor for their proper functioning in converting pyrophosphate to orthophosphate.…”

Fundamental Cell Morphologies Examined With Cryo-TEM of the Species in the Novel Five Genera Robustly Correlate With New Classification in Family Mycobacteriaceae

“…Although some studies dispute the novel classification of the family Mycobacteriaceae ( Nouioui et al, 2018 ; Tortoli et al, 2019 ), others use basonyms ( Brzeszcz and Kaszycki, 2018 ; Chevtchouk Jurno et al, 2019 ), or another study interpreted five novel genera as sub-genera ( Bachmann et al, 2019 ; Matsumoto et al, 2019 ), the literature supported and used the novel classification ( Ito et al, 2018 ; Yamada et al, 2018 ; Cereija et al, 2019 ; Del Barrio-Duque et al, 2019 ; Kim et al, 2019 ; Sánchez et al, 2019 ; Tiago et al, 2019 ; Zhou et al, 2019 ; Chin et al, 2020 ; Salam et al, 2020 ; Tan et al, 2020 ). This work reflects comparative morphological studies by Gupta et al (2018) .…”